Serotonin is a primary neurotransmitter with several diverse functions, including a proposed important role in depression and in the mediation of some of ethanol's effects. This study was conducted in order to elucidate the nature of the circuitry of the serotonergic system via simultaneous monitoring of serotonin levels in the cell body region of the raphe nuclei and the terminal region of the frontal cortex. Manipulations of serotonin were made via focal infusion of the serotonin reuptake inhibitor and antidepressant fluoxetine, into either region and subsequent changes in the other area were determined. Regionally applied fluoxetine increased local serotonin levels about four-fold in either structure, with an accompanying concurrent minor change of serotonin levels, usually a decrease, in the other brain region studied. Furthermore the response of both regions to a systemic injection of the same serotonin reuptake inhibitor showed a disocciation, with serotonin in the raphe region increasing significantly in response to fluoxetine whilst more modest changes or even a decrease in the cortical region in response to the same injection. Current research is focussing on the possible serotonin receptor subtypes mediating these responses with a proposed course to study possible adaptational changes in chronic fluoxetine and alcohol treated rats.